Glaucoma remains one of the leading causes of blindness in the United States, yet the abnormality causing the disease has not been identified. In spite of intensive study, the normal channels by which fluid leaves the eye and the mechanisms by which aqueous outflow is controlled have not been satisfactorily defined. The present applicant and others have recently demonstrated an exquisite pressure-sensitive mobility of the trabecular meshwork. Systematic control of this mobility has demonsrated that the trabecular meshwork comes into apposition to the external wall of Schlemm's canal at high pressure; a phenomenon previously postulated to occur as an abnormality in glaucoma on the basis of physiology studies. In addition, pressure control has implicated channels through endothelial tubules as the mechanism for aqueous outflow, and has permitted identification of a previously-unsuspected elastic-contractile behavior of the endothelium lining Schlemm's canal. We want to determine how mechanical and pharmacologic manipulations known to alter aqueous outflow achieve their effect. We will seek evidence of their ability to regulate anatomic relationships such as the relationship of the trabecular meshwork to the external wall of Schlemm's canal. We want to further document the role of the endothelial tubules of Schlemm's canal as channels for aqueous flow. We also want to further define the elastic-contractile behavior of the endothelial lining of Schlemm's canal that might represent a mechanism for regulation of aqueous outflow. We plan to continue our studies of aqueous dynamics by correlating precisely-controlled physiologic parameters of pressure and flow with anatomic information from light, scanning and transmission electron microscopy. It is expected that information gained from these studies can be directly applied to identifying the cause of open angle glaucoma, resulting in eventual improved treatment of the disease.